As a means of obtaining more efficient immunotherapy of tumors, we are investigating possible methods for increasing the cytotoxicity of antibodies. Antitumor antibodies have been conjugated to various toxic agents such as radioactive iodine, diphtheria toxin and nitrogen mustards. The toxicity of the conjugates is being evaluated with tumor cells in tissue culture. We are also investigating the cytotoxicity of antibody-enzyme conjugates with the expectation that we can utilize the catalytic activity of the enzyme to convert a protoxin substrate to a toxin. Toxin- or enzyme-antibody conjugates which appear promisng in vitro will be investigated in vivo in experimental animals. We are studying the effects of antibodies on tumor cell metabolism and growth both in vivo an in vitro. We are also attempting to amplify the reactivity of lymphocytes for target tumor cells.